Mefloquine was widely prescribed to U.S. military service members until 2009 when use was limited to personnel with contraindications to doxycycline and no contraindications to mefloquine. The need to estimate the occurrence of neuropsychiatric outcomes (NPOs) in service members prescribed mefloquine warranted a comprehensive evaluation of this issue. Active component service members filling a prescription for mefloquine, doxycycline, or atovaquone/proguanil (A/P) between January 1, 2008 and June 30, 2013, were included in the analysis. The risk of developing incident NPOs and the risk of subsequent NPOs among subjects with a history of the condition were assessed. A total of 367,840 individuals were evaluated (36,538 received mefloquine, 318,421 received doxycycline, and 12,881 received A/P). Among deployed individuals prescribed mefloquine, an increased risk of incident anxiety was seen when compared with doxycycline recipients (incidence rate ratio [IRR] = 1.12 [1.01-1.24]). Among nondeployed mefloquine recipients, an increased risk of posttraumatic stress disorder (PTSD) was seen when compared with A/P recipients (IRR = 1.83 [1.07-3.14]). An increased risk of tinnitus was seen for both deployed and nondeployed mefloquine recipients compared with A/P recipients (IRR = 1.81 [1.18-2.79]), 1.51 (1.13-2.03), respectively). Six percent of the mefloquine cohort had an NPO in the year before receiving mefloquine. When comparing individuals with a prior neuropsychiatric history to those without, the ratio of relative risks for adjustment disorder, anxiety, insomnia, and PTSD were higher (not statistically significant) for mefloquine compared with doxycycline. These findings emphasize the continued need for physicians prescribing mefloquine to conduct contraindication screening.
